We propose to develop diagnostic tools for the early detection of chronic disease of airways and to study mechanisms which cause attacks of asthma. The physiologic studies of early diagnosis aim to develop specific and sensitive tests for early detection of chronic airway obstruction (including the use of a new, rapid CO meter) and to determine the anatomic basis of the physiologic abnormalities. The radiologic studies aim to establish the safety and efficacy of powdered tantalum as a bronchographic contrast material for detecting early airway disease, to simplify its administration so it can be used as a simple screening test for abnormal airway structure and for identifying sites of abnormal mucociliary clearance. Because airway hyperirritability appears to be closely linked to the precipitation of asthma attacks, we will perform clinical studies to determine the role of epithelial damage in the development of sensitivity of bronchi in subjects exposed to respiratory viruses, ozone, and other industrial and ambient pollutants. We will analyze the neurophysiologic and anatomic basis of our clinical findings in a series of animal experiments. Because interactions between humoral and autonomic nervous mechanisms also appear to play an important role in the pathogenesis of asthma, we will utilize neurophysiologic, immunologic, pharmacologic and anatomic methods to investigate these mechanisms in experimentally-induced canine asthma.